Benhur Godoi

Regioselective synthesis of isochromenones by iron(III)/PhSeSePh-mediated cyclization of 2-alkynylaryl esters.

A series of 4-Se-(Te, S)-isochromenones and 3-substituted isochromenones were synthesized in good yields via FeCl(3)-mediated cyclization of alkynylaryl esters with different diorganyl dichalcogenides. This methodology was carried out at room temperature, using inexpensive and environmentally friendly iron salts as metallic source and under air atmosphere. The reaction showed to be tolerant to a range of substituents bonded into the aromatic ring of the diorganyl dichalcogenides as well as to alkyl groups directly bonded to the chalcogen atom. Alternatively, the cyclization reaction of 2-alkynylaryl esters with FeCl(3), in the absence of diorganyl dichalcogenide, gave the isochromenones without the chalcogen moiety in the structure. This approach proved to be highly regioselective, providing only six-membered ring products, once the possible five-membered products were not observed in any experiments.

Synthesis of Organochalcogen Propargyl Aryl Ethers and Their Application in the Electrophilic Cyclization Reaction: An Efficient Preparation of 3-Halo-4-Chalcogen-2H-Benzopyrans

We herein described the synthesis of various organochalcogen propargyl aryl ethers via reaction of lithium acetylide intermediate with electrophilic chalcogen (sulfur, selenium, tellurium) species. Various aryl and alkyl groups directly bonded to the chalcogen atom were used as electrophile. The results revealed that the reaction does not significantly depend on the electronic effects of substituents in the aromatic ring bonded to the chalcogen atom of the electrophilic chalcogen species. Additional versatility in this process was demonstrated with respect to a diverse array of functionality in the aromatic ring at propargyl aryl ethers. These propargyl aryl ethers, bearing the chalcogen group, underwent highly selective intramolecular cyclizations when treated with I(2) or ICl affording 3-iodo-4-chalcogen-2H-benzopyrans. The results demonstrated that the cyclization efficiency was significantly influenced by the steric effects of aromatic ring, since the cyclization reaction gave low yields with aromatic rings having a substituent at orto position than those having no substituent. The reactivity of 3-iodo-4-chalcogen-2H-benzopyrans was also studied. 4-Selenobutyl benzopyrans were treated under Neghishi cross-coupling conditions providing the corresponding 3-aryl benzopyran derivatives in good yields. In addition, using the copper catalyzed cross-coupling reactions with thiols, in the absence of any cocatalyst, we were able to introduce a thiol function in 3-iodo-benzopyran derivatives.

Iron(III) Chloride/Diorganyl Diselenides: A Tool for Intramolecular Cyclization of Alkynone O-Methyloximes

This report describes the synthesis of 4-organoselenylisoxazoles via FeCl(3)/RSeSeR-mediated intramolecular cyclization of alkynone O-methyloximes. The optimized conditions allowed the cyclization to proceed at room temperature under ambient atmosphere, and the reaction requires a short time to be completed. The reaction conditions tolerated neutral, electron-donating and electron-withdrawing groups present in both substrates, alkynone O-methyloximes and diorganyl diselenides. Treatment of 4-organoselenylisoxazoles with n-butyllithium, followed by trapping with electrophiles, furnished the functionalized isoxazoles in good yields. The obtained products also proved to be suitable substrates for the preparation of 4-bromoisoxazoles via Br/Se exchange reaction.

The antidepressant-like action of a simple selenium-containing molecule, methyl phenyl selenide, in mice.

Selenium-containing molecules show promising pharmacological properties. The antidepressant-like action of CH(3)SePh in the mouse forced swimming test (FST) and the tail suspension test (TST), models predictive of depressant activity, were investigated in this study. Moreover, the involvement of dopaminergic system in the antidepressant-like action of CH(3)SePh was studied. The behavioral results showed that CH(3)SePh significantly reduced the immobility time in the FST (25 and 50 mg/kg, intragastrically; i.g.) and the TST (50 mg/kg, i.g.), without accompanying changes in ambulation when assessed in the open-field test (OFT). The anti-immobility effect of CH(3)SePh (50 mg/kg, intragastrically; i.g.) in the FST was prevented by pretreatment of mice with haloperidol (0.2 mg/kg, i.p., a dopamine D(2) receptor antagonist), SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D(2) and D(3) antagonist). These results suggest that CH(3)SePh produced an antidepressant-like action in the mouse FST and TST. The antidepressant-like action of CH(3)SePh, a simple selenium-containing molecule, seems most likely to be mediated through an interaction with the dopaminergic system.

m-Trifluoromethyl-diphenyl diselenide attenuates pentylenetetrazole-induced seizures in mice by inhibiting GABA uptake in cerebral cortex slices

The present study investigated the anticonvulsive effect of the disubstituted diaryl diselenides diphenyl diselenide (PhSe)(2), m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on a chemical model of seizure induced by pentylenetetrazole (PTZ) in mice. (PhSe)(2), (p-Cl-C(6)H(4)Se)(2) and (p-CH(3)O-C(6)H(4)Se)(2) did not abolish seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) at the dose of 100 mg/kg significantly prolonged the latency of the onset of the first convulsive episode and reduced the number of animals that presented seizures. To investigate the possible mechanisms involved in the anticonvulsant effect of (m-CF(3)-C(6)H(4)Se)(2), mice were submitted to different associations (all drugs in a sub-effective dose); aminooxyacetic acid hemihydrochloride (AOAA, a gamma-aminobutyric acid (GABA)-T inhibitor), diazepam (a GABA(A) receptor agonist) or DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake) were pre-administered together with (m-CF(3)-C(6)H(4)Se)(2). (m-CF(3)-C(6)H(4)Se)(2) + DABA abolished seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) administered alone or with PTZ decreased the levels of GABA uptake in cerebral cortex slices. The present study demonstrates that (m-CF(3)-C(6)H(4)Se)(2) exerts anticonvulsant action by decreasing the levels of GABA uptake.

Organoselenium compounds from purines: Synthesis of 6-arylselanylpurines with antioxidant and anticholinesterase activities and memory improvement effect

We describe here a simple method for the synthesis of 6-arylselanylpurines with antioxidant and anticholinesterase activities, and memory improvement effect. This class of compounds was synthesized in good yields by a reaction of 6-chloropurine with diaryl diselenides using NaBH4 as reducing agent and PEG-400 as solvent. Furthermore, the synthesized compounds were evaluated for their in vitro antioxidant and acetylcholinesterase (AChE) inhibitor activities. The best AChE inhibitor was assessed on the in vivo memory improvement. Our results demonstrated that the 6-((4-chlorophenyl)selanyl)-9H-purine and 6-(p-tolylselanyl)-9H-purine presented in vitro antioxidant effect. In addition, 6-((4-fluorophenyl)selanyl)-9H-purine inhibited the AChE activity and improved memory, being a promising therapeutic agent for the treatment of Alzheimers disease.